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Antimicrobial Agents and Chemotherapy, August 2006, p. 2626-2631, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.01165-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Comparative Pharmacodynamics of Gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa

Vincent H. Tam,^* Samer Kabbara, Giao Vo, Amy N. Schilling, and Elizabeth A. Coyle

University of Houston College of Pharmacy, Houston, Texas

Received 6 September 2005/ Returned for modification 4 December 2005/ Accepted 31 May 2006

Aminoglycosides are often used to treat severe infections with gram-positive organisms. Previous studies have shown concentration-dependent killing by aminoglycosides of gram-negative bacteria, but limited data are available for gram-positive bacteria. We compared the in vitro pharmacodynamics of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa. Five S. aureus strains were examined (ATCC 29213 and four clinical isolates). Time-kill studies (TKS) in duplicate (baseline inocula of 10⁷ CFU/ml) were conducted to evaluate bacterial killing in relation to increasing gentamicin concentrations (0 to 16 times the MIC). Serial samples were obtained over 24 h to quantify bacterial burden. Similar TKS with P. aeruginosa ATCC 27853 were conducted, and the time courses of the all bacterial strains were mathematically modeled for quantitative comparison. A dose fractionation study (using identical daily doses of gentamicin) in an in vitro hollow-fiber infection model (HFIM) over 5 days was subsequently used for data validation for the two ATCC strains. Model fits to the data were satisfactory; r² values for the S. aureus and P. aeruginosa ATCC strains were 0.915 and 0.956, respectively. Gentamicin was found to have a partially concentration-dependent killing effect against S. aureus; concentrations beyond four to 8 times the MIC did not result in significantly faster bacterial killing. In contrast, a concentration-dependent profile was demonstrated in suppressing P. aeruginosa regrowth after initial decline in bacterial burden. In HFIM, thrice-daily gentamicin dosing appeared to be superior to once-daily dosing for S. aureus, but they were similar for P. aeruginosa. Different killing profiles of gentamicin were demonstrated against S. aureus and P. aeruginosa. These results may guide optimal dosing strategies of gentamicin in S. aureus infections and warrant further investigations.

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* Corresponding author. Mailing address: University of Houston College of Pharmacy, 1441 Moursund Street, Houston, TX 77030. Phone: (713) 795-8316. Fax: (713) 795-8383. E-mail: vtam{at}uh.edu.

Supplemental material for this article may be found at http://aac.asm.org/.

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Antimicrobial Agents and Chemotherapy, August 2006, p. 2626-2631, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.01165-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Tam, V. H., Ledesma, K. R., Vo, G., Kabbara, S., Lim, T.-P., Nikolaou, M. (2008). Pharmacodynamic Modeling of Aminoglycosides against Pseudomonas aeruginosa and Acinetobacter baumannii: Identifying Dosing Regimens To Suppress Resistance Development. Antimicrob. Agents Chemother. 52: 3987-3993 [Abstract] [Full Text]